The present invention relates to apparatus and methods for delivering drugs or other beneficial agents. More specifically, the present invention relates to iontophoretic electrotransport devices and methods of their use in delivering treatment to a body.
Iontophoretic transport of drug or biological treatments is well known, and is commonly used as one way to transport such treatments across a surface and into a body. Many iontophoretic devices have been developed, as witnessed by the quantity of issued patents and pending applications mentioning such phenomena. A representative such application, titled xe2x80x9cRate adjustable drug delivery systemxe2x80x9d filed by Birch Point Medical, Inc., was published Jul. 12, 2001 as international publication No. WO 01/49365 A1. The ""49365 application is hereby incorporated by this reference as though set forth in full herein.
Existing iontophoretic devices may generally be classified into two groups based upon their electromotive source. The first such group may be characterized as disposable, and are driven by a galvanic or electrochemical reaction encompassing electrodes bathed in an electrolyte carrying the treatment ions and offering a relatively low voltage. Such devices inherently require long treatment time intervals. Such devices are also generally constructed to be inexpensive, used once, and then thrown away. The second type of iontophoretic device typically is driven by an auxiliary power module. While treatment time requirements for devices having auxiliary power modules are generally reduced, the power modules are expensive, and so typically must be reused.
A representative disposable device, generally indicated at 30 in FIG. 1, can be constructed on an adhesive strip 33. Cationic chamber 35 and anionic chamber 37 are formed in the adhesive strip 33 to create separated volumes in which to house cationic and anionic treatment materials, respectively. An electrolytic cell created by a chemical reaction between the cationic and anionic electrodes in an electrolyte provides the electromotive force to operate the device for ion transfer to a patient. A first electrode 39 installed in the cationic chamber and a second electrode 41 installed in the anionic chamber are connected by a conductor 43 to form an electron transporting leg of an electric circuit. Application of the adhesive strip to a human body completes the circuit, and initiates a flow of treatment ions through the patient""s skin.
An electrode 39 maybe formed from zinc, with an electrode 41 being made from silver chloride. The electrolyte contained in the cationic chamber 35 and anionic chamber 37 directly contacts the skin to be treated, and necessarily is limited in reactivity to avoid skin irritation. Conductive salt solutions (such as 1% NaCl) commonly are employed as electrolytes due to their compatibility with a patient""s skin. A device 30, as described, will generate an electromotive force for ion transfer totalling about 1 Volt. In use of a device 30, there is some possibility that a desired treatment chemical may undesirably interact with the electrolyte, electrode, or a product of the galvanic reaction, thereby compromising a treatment.
An alternative construction of a disposable type device is generally indicated at 50 in FIG. 2. As a way to increase the voltage between the cationic chamber 35 and anionic chamber 37, a plurality of galvanic cells may be arranged in electrical series on an adhesive strip 33. Two such cells are illustrated in the embodiment 50. A first electrode 39 in the cationic chamber 35 is connected in series to electrode 53 in cell 55. Electrode 57, also housed in cell 55, is then connected in series to electrode 59 in cationic chamber 37. Such a two cell arrangement can effectively double the voltage generated by the device, and can therefore reduce a length of treatment time required. Additional cells may be added in series, however, the adhesive strip 33 rapidly becomes crowded, thereby limiting the practical range in electromotive force for a device 30.
FIG. 3 illustrates an exploded cross-section view through a device 30. As illustrated, the cationic chamber 35 and anionic chamber 37 typically are open toward the patient. Some sort of substrate 59 typically is provided as a receptor to hold the treatment chemicals (beneficial agent) or electrolyte in a chamber prior to installation of adhesive strip 33 onto a patient. Substrates 59 typically are made from gauze, cellulose, cotton, or other hydrophilic material. It is common practice to saturate the substrates 59 just prior to attaching an adhesive strip 33 to a patient for a treatment session. Substrates 59 may be loaded with treatment substances using a syringe or any other convenient transfer implement.
A representative device driven by a reusable auxiliary power module is illustrated generally at 60 in FIG. 4. A power module 63 typically houses sophisticated electronics, and is relatively expensive (power modules are generally not regarded as single use, disposable items). Power module 63 may provide a substantial voltage to cause ion migration through a body. Applied voltages may reach perhaps 90 Volts, although perhaps for only a very short period of time to initiate ion transfer. Depending upon the skin contact area for ion transfer from a treatment chamber and the composition of the beneficial agent, a patient may perceive a burning sensation under an applied voltage of only 30 volts. Power modules maybe attached directly to an adhesive strip 33, as illustrated, but are more commonly connected in-circuit between the cationic chamber 35 and anionic chamber 37 using wires, or extension leads 65, to permit some degree of motion for a patient undergoing a treatment.
The electronics portion of a power module 63 may be constructed to generate a range of voltages, hold a voltage substantially constant for a period of time, or cause a programmable range in voltage over a period of time. Similar modulation may be made by a power module 63 to a current flowing in the circuit. However, power modules 63 represent an expense and may cause inconvenience in that operators may require special expertise to properly configure the module for a particular treatment.
A patient would benefit from a simple, disposable, iontophoretic device capable of higher voltage and more sustained current transmission than commercially available disposable devices, but being less costly than devices requiring an electronic module. An improvement in current transmission to minimize a polarization effect in commercially available disposable devices would also be an advance. A disposable iontophoretic device having a treatment time operably controlled by the working life of a disposable power source having a square-wave current flow would be an additional advance.
The invention provides an apparatus and method for delivering a treatment to a body by way of an iontophoretic transport procedure. A device constructed according to principles of the instant invention provides a low cost, disposable, single use, fast and accurate, iontophoretic fluid delivery device for external or implantable use. A body may be construed specifically as a mammalian (e.g. human or animal) body, or alternatively and generally, as a container of an electrolyte. A treatment to be applied to a body by the instant device and method may be either cationic-based, or anionic-based.
An iontophoretic fluid delivery device within contemplation typically includes a cationic chamber, an anionic chamber, and an electromotive force to promote ion exchange between a body and one or both of the chambers. The cationic and anionic chambers define separate volumes in which are held cationic and anionic substances, respectively. A wall of each chamber provides a passageway, or opening, through which ions may migrate. The passageways are generally oriented and arranged on a surface of a container to enable creation of a first conductive path, through a cooperating body, of an electrical circuit between the cationic and anionic chambers.
Treatment materials may be loaded, by syringe or other transfer mechanism, onto a substrate housed within a chamber. Substrates desirably may be configured to reduce polarization of the treatment materials and an attendant drop in reaction rate. One such configuration includes an electrically conductive substrate affixed to a wall of one of the chambers. A workable such substrate may have a surface area, for electron transfer, sized substantially in correspondence with an opening of an ion transfer passageway. An alternate substrate may be formed as an electrically conductive gauze. The conductive gauze may be dispersed substantially throughout the volume of the chamber. A hydrogel substance operable as an electrolyte can be disposed, substantially as a pre-loaded item, in one or both of the cationic or anionic chambers. Such a pre-loaded hydrogel can reduce preparation time of a treatment by requiring only the treatment to be introduced, and only to a single chamber of the container.
Devices operable primarily as anionic treatment devices may be made to have a color, texture, shape, or size to differentiate them from a cationic treatment device. Furthermore, individual chambers housed by a container may be made to have different sizes or shapes to facilitate identification and loading of treatment materials into the correct chamber.
One exemplary container can be embodied as an adhesive strip or patch. Alternatively, the container may be a cartridge, carton, or tube for insertion into a body. Devices adapted for insertion into a body, or adapted for storage in preloaded form, may include semipermeable membranes disposed as passageway coverings to contain treatment substances within separate chambers prior to use of a container during a therapeutic treatment.
The electromotive force required to operate the device desirably is supplied by an electromotive cell (such as a self-contained mini battery), located in a second electrically conductive path configured to complete the electrical circuit between the cationic and anionic chambers. Preferred cells will have an approximately square-wave current discharge over their working life. Serviceable electromotive cells may be constructed containing electro-chemically reactive matter in an amount operable to control a length in time of the cell""s working life. Furthermore, the operable or working life of the electromotive cell desirably is set to be in harmony with the desired treatment time, and can therefore be used as a measurement control to resist over treating of a patient. The working life of battery may be determined or manipulated by circuit elements such as a shunting resistor in a circuit parallel to an ion conducting path. Electromotive cells within contemplation nonexclusively include mini batteries constructed to operate with a metal-anode based electrochemical reaction using lithium, zinc, magnesium, or aluminum. Such self-contained mini batteries can be made rugged to withstand incidental abuse without incurring sufficient damage to suffer a leak of their contents. Such batteries may also be made in a thin and flexible form to reduce container bulk.
Certain preferred iontophoretic devices may use one or more electromotive cells, as required, e.g. to control a length of time for, or rate of, delivery of a quantity of a treatment ion to a body. Such cells may be located partially or completely inside either one or both chambers, or attached to the container in some convenient location. In addition to providing treatment control through their inherent operating life, cells may be arranged in series to provide an increased voltage over a single cell. The increased voltage may permit a reduction in a time of treatment application.
A cell located partially, or totally, within a chamber generally includes a fluid resistant barrier to isolate an electrolytic path between the cell""s positive and negative poles. In such case, a portion of either a positive or a negative pole may be exposed for electron transfer directly to an electrolyte. The cell housing may optionally be formed from, or coated with, a noble or inert metal to avoid its undergoing an undesirable chemical reaction with treatment chemicals. Alternatively, an inert metal may be placed, as an electron interface for the electrochemical reaction, in-circuit between an exterior cell and interior treatment chemicals or fluids. Of course, other conductive metals or alternative conducting materials may be employed in situations where a reaction between the conductive material and treatment fluids would not be detrimental.
One embodiment of the instant invention includes a first electromotive cell disposed interior to the cationic chamber. The first cell has an electrolyte barrier exposing only a portion of its negative pole. A second cell, in electrical series with the first cell, may be included interior to the anionic chamber. The second cell also has an electrolyte barrier, but exposing a portion of its positive pole. A conductive path between the two cells is generally sealed to resist transmission of electrolyte from or between the chambers. The invention may alternatively include a single electromotive cell, located in either of the chambers, as desired and practical. In another arrangement, the single electromotive cell may be affixed to container structure separate from both chambers. An embodiment may have electromotive cells located in each chamber, and with one or more additional cells located exterior the chambers and attached to structure of the container. An arrangement of subcells adjacently stacked in electrical series may be regarded as single electromotive cell for purpose of packaging in a chamber, or on a container.
One or more additional circuit components may be included in the second conductive path to increase treatment options and efficacy. As a non-limiting example, an oscillator element can be disposed in-circuit in the second conductive path and operate to control a current flow between high and low values. A manual or automatic switch placed in the second path may be used to start and stop treatments at controlled intervals. A Light Emitting Diode (LED) may be placed in the second path to provide a visual indicator showing status of the treatment. When such LED is producing a visible output, a patient can be confident that the treatment is proceeding. When the LED no longer produces a visible output, the patient can be confident that the treatment is concluded. An electronic component capable of dissipating electric energy in the form of heat may advantageously be placed in a position operable to heat the contents of a chamber, such as a treatment fluid. Warming the treatment fluid or agent can increase a rate of reaction or solubility of a treatment substance, improving efficacy of the device.
One method of using the instant device, for iontophoretic treatment of a patient, includes the steps of: a) providing an iontophoretic fluid delivery device having a cationic chamber and an anionic chamber, one of the chambers containing a hydrogel; b) adding a fluid only to one of the chambers to form an electrolyte treatment; and c) affixing the device to a surface of a patient""s body for a duration of time as required to transfer a desired quantity of treatment to the patient.
These features, advantages, and alternative aspects of the present invention will be apparent to those skilled in the art from a consideration of the following detailed description taken in combination with the accompanying drawings.